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Completed

NCT Number: NCT02992899

Closed Loop Vagal Nerve Stimulation for Patients With Posttraumatic Stress Disorder

The tasks of the project are to map the potency and kinetics of the neurologic, autonomic peripheral, inflammatory, and behavioral responses to vagal nerve stimulation (VNS) vs. sham treatment, at baseline and in response to stressful traumatic scripts related to personal traumatic events, as well as a series of other stressors.

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Key information

Conditions

Posttraumatic Stress Disorder Mental Disorders Stress Disorders, Post-Traumatic Stress Disorders, Traumatic Trauma and Stressor Related Disorders

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Emory University

Atlanta, Georgia, 30322, United States

About this study

The purpose of this project is to develop the fundamental physiological understanding of feedback controlled vagal nerve stimulation (VNS) using positron emission tomography (PET) brain imaging and blood biomarker measurement with stress in healthy individuals and individuals with PTSD. Healthy human subjects with a history of psychological trauma but without the diagnosis of a psychiatric disorder (Phase 1), and human subjects with a history of PTSD (Phase 2), undergo PET imaging of the brain in conjunction with VNS or a sham treatment during exposure to neutral scripts and scripts of personal traumatic events. Blood is drawn simultaneously for measurement of a variety of stress responsive biomarkers, including inflammatory markers and neurohormones. A second PET scan with biomarkers assesses the delayed effects of VNS. On two other days subjects undergo exposure to random stressors with VNS or sham in conjunction with measurement of stress biomarkers.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Phase 1:

  • Do not meet criteria for post traumatic stress disorder (PTSD) or other major mental disorder as determined by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5 SCID) interview for PTSD
  • Have a history of psychological trauma as defined by DSM-5.

Phase 2:

  • Meet criteria for PTSD as determined by the Structured Clinical Interview for DSM-5 (SCID) interview for PTSD.

Exclusion criteria

  • Positive pregnancy test
  • Meningitis
  • Traumatic brain injury
  • Neurological disorder or organic mental disorder
  • History of loss of consciousness greater than one minute
  • Alcohol abuse or substance abuse or dependence based on the SCID within the past 12 months
  • Positive toxicology screen
  • Current or lifetime history of schizophrenia, schizoaffective disorder, or bulimia, based on the SCID
  • A history of serious medical or neurological illness, such as cardiovascular, gastrointestinal, hepatic, renal, neurologic or other systemic illness
  • Evidence of a major medical or neurological illness on physical examination or as a result of laboratory studies (complete blood count (CBC), blood urea nitrogen (BUN), creatinine, blood sugar, electrolytes, liver and thyroid function tests, urinalysis, and EKG)
  • Active implantable device (i.e. pacemaker)
  • Carotid atherosclerosis
  • Cervical vagotomy

Treatment and study plan

GammaCore/electroCore non-invasive VNS device

Device

Vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The intensity of the stimulus (the current amplitude) is adjusted by the user, to the maximum tolerable level to ensure VNS without causing excessive pain (typically 10-30 V), the burst frequency to 5 kilohertz (kHz), and the envelope frequency to 25 Hz. These are the standard frequency settings that electroCore has demonstrated to be most effective in capturing the vagus nerve based on evoked potential studies. The duration of delivery is 2 minutes, one minute into which the high-resolution positron emission tomography (HR-PET) scan is conducted; following an additional 8 minutes, a second VNS delivery is administered, after which another scan is obtained.

Sham gammaCore/electroCore

Device

Sham vasal nerve stimulation (VNS) is self-administered using the electroCore non-invasive VNS device. The device is programmed such that no actual stimulation is given to the vagus nerve. The duration of delivery is 2 minutes, one minute into which the HR-PET scan is conducted; following an additional 8 minutes, a second sham VNS delivery is administered, after which another scan is obtained.

O-15 Water

Drug

Oxygen-15 labelled water is a radioactive variation of regular water, in which the oxygen atom has been replaced by oxygen-15 (15O), a positron-emitting isotope. 15O-water is used as a radioactive tracer for measuring and quantifying blood flow using positron emission tomography (PET) . H2[15O] will be prepared on-site in the Emory PET Center cyclotron. During the hours of the test, an intravenous infusion of normal saline will be started to permit the bolus injection of H2[15O]. Subjects will receive a 20 mCi intravenous bolus of H2[15O] for each of the 14 scans during exposure to neutral and traumatic scripts.

Primary outcomes

  1. Level of Interleukin-6 (IL6)

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    IL6 level will be collected via blood draw. Change is defined as the difference in IL6 level from baseline to post emotional stress testing.

Secondary outcomes

  1. Level of Tryptophan

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Tryptophan level will be collected via blood draw. Change is defined as the difference in tryptophan level from baseline to post emotional stress testing.

  2. Level of Kynurenine

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Kynurenine level will be collected via blood draw. Change is defined as the difference in kynurenine level from baseline to post emotional stress testing.

  3. Level of Kynurenic Acid

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Kynurenic acid level will be collected via blood draw. Change is defined as the difference in kynurenic acid level from baseline to post emotional stress testing.

  4. Level of 3-3 Hydroxykynurenine

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    3-3 hydroxykynurenine level will be collected via blood draw. Change is defined as the difference in 3-3 hydroxykynurenine level from baseline to post emotional stress testing.

  5. Level of Anthranilic Acid

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Anthranilic Acid level will be collected via blood draw. Change is defined as the difference in anthranilic acid level from baseline to post emotional stress testing.

  6. Level of Tumor Necrosis Factor (TNF)-Alpha

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    TNF-alpha level will be collected via blood draw. Change is defined as the difference in TNF-alpha level from baseline to post emotional stress testing.

  7. Level of Interferon-Gamma

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Interferon-Gamma level will be collected via blood draw. Change is defined as the difference in Interferon-Gamma level from baseline to post emotional stress testing.

  8. Level of Interleukin-1 Beta

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Interleukin-1 Beta level will be collected via blood draw. Change is defined as the difference in Interleukin-1 Beta level from baseline to post emotional stress testing.

  9. Level of Interleukin-2 (IL2)

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    IL2 level will be collected via blood draw. Change is defined as the difference in IL2 level from baseline to post emotional stress testing.

  10. Level of Interleukin-4 (IL4)

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    IL4 level will be collected via blood draw. Change is defined as the difference in IL4 level from baseline to post emotional stress testing.

  11. Level of Interleukin-8 (IL8)

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    IL8 level will be collected via blood draw. Change is defined as the difference in IL8 level from baseline to post emotional stress testing.

  12. Level of Interleukin-10 (IL10)

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    IL10 level will be collected via blood draw. Change is defined as the difference in IL10 level from baseline to post emotional stress testing.

  13. Level of Interleukin-12p70 (IL12p70)

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    IL12p70 level will be collected via blood draw. Change is defined as the difference in IL12p70 level from baseline to post emotional stress testing.

  14. Level of Interleukin-12p (IL12p)

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    IL12p level will be collected via blood draw. Change is defined as the difference in IL12p level from baseline to post emotional stress testing.

  15. Level of Interleukin-13 (IL13)

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    IL13 level will be collected via blood draw. Change is defined as the difference in IL13 level from baseline to post emotional stress testing.

  16. Level of Macrophage Migration Inhibitory Factor

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Macrophage migration inhibitory factor will be collected via blood draw. Change is defined as the difference in factor level from baseline to post emotional stress testing.

  17. Level of High-Mobility Group Protein B1

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    High-mobility group protein B1 level will be collected via blood draw. Change is defined as the difference in high-mobility group protein B1 level from baseline to post emotional stress testing.

  18. Level of Adrenocorticotropic Hormone

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Adrenocorticotropic hormone level will be collected via blood draw. Change is defined as the difference in adrenocorticotropic hormone level from baseline to post emotional stress testing.

  19. Level of Cortisol

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Cortisol level will be collected via blood draw. Change is defined as the difference in cortisol level from baseline to post emotional stress testing.

  20. Level of Epinephrine

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Epinephrine level will be collected via blood draw. Change is defined as the difference in epinephrine level from baseline to post emotional stress testing.

  21. Level of Dopamine

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Dopamine level will be collected via blood draw. Change is defined as the difference in dopamine level from baseline to post emotional stress testing.

  22. Level of Norepinephrine

    Time frame: Baseline, Post Stress Testing (Up to 4 Hours)

    Norepinephrine level will be collected via blood draw. Change is defined as the difference in norepinephrine level from baseline to post emotional stress testing.

Sponsors and collaborators

Lead sponsor

Emory University

Other

Collaborators

  • Georgia Institute of Technology

Registry information

Official study title

Closed Loop Vagal Nerve Stimulation in Patients With Posttraumatic Stress Disorder

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Dec 14, 2016
Registry last updated
Jun 14, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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